Fig. 2.

Changes in metabolic and behavior phenotypes, transcriptome, DNA methylome, and biological pathways in response to fructose treatment and DHA supplementation. (a) Metabolic and behavior phenotypes. From left to right: blood glucose, serum triglycerides, serum insulin, insulin resistance index, and latency time in the memory retention probe in the Barnes Maze test. Fructose group was compared with the control group, and the fructose + DHA group was compared to the fructose only group. ^⁎p < 0.01 and ^#p < 0.05 by 2-sided Student's t-test. Error bars in the plots are standard errors. N = 8/group. (b) Heatmap of gene expression changes in hypothalamus and hippocampus. Blue to red colors indicate low to high expression values. (c) Heatmap of DNA methylation changes in hypothalamus and hippocampus. Blue to red colors indicate low to high methylation levels. (d) Select biological pathways affected by fructose and DHA in hypothalamus and hippocampus. Bars are the –log10 enrichment p values of the pathways. The insert plot on the right shows the opposite direction of changes in genes in the “focal adhesion” pathway in the hypothalamus between fructose and DHA: fructose mostly inhibits whereas DHA reverses the expression levels. In the insert plot Y-axis indicates log10 fold changes. The fructose + DHA group is labeled as F + D in panels b–d.